A5067543754- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- MicroRNA in disease regulation
- Genomics, phytochemicals, and oxidative stress
- interferon and immune responses
- Immunodeficiency and Autoimmune Disorders
- Single-cell and spatial transcriptomics
- Photochemistry and Electron Transfer Studies
- Mast cells and histamine
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Viral Infections and Outbreaks Research
- Viral Infectious Diseases and Gene Expression in Insects
- Renal cell carcinoma treatment
- Protein Interaction Studies and Fluorescence Analysis
- Polyomavirus and related diseases
- Kruppel-like factors research
- Atherosclerosis and Cardiovascular Diseases
- Silicon Carbide Semiconductor Technologies
- Tuberous Sclerosis Complex Research
The University of Texas Southwestern Medical Center
2021-2025
Southwestern Medical Center
2021-2024
Southwestern University
2024
University of Colorado Anschutz Medical Campus
2021
National Human Genome Research Institute
2016-2021
National Institutes of Health
2015-2021
National Institute of Allergy and Infectious Diseases
2019-2021
University of Colorado Denver
2021
Emory University
2012-2017
National Institute of Biological Sciences, Beijing
2010
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as cell exhaustion. Although it is well recognized that memory CD8 account for the persistence of immunity after acute infection, how exhausted persist remains less clear. Using infection with lymphocytic choriomeningitis virus clone 13 tumor samples, we demonstrate differentiate into TCF1high more TCF1low population. Virus-specific cells, which resemble follicular helper (TFH) recall better than do...
Regulatory T cells (T regs ) accumulate in the visceral adipose tissue (VAT) to maintain systemic metabolic homeostasis but decline during obesity. Here, we explored pathways controlling homeostasis, composition, and function of VAT under normal high-fat diet feeding conditions. We found that cholesterol metabolism was specifically up-regulated ST2 hi reg subsets. -specific deletion Srebf2 , master regulator selectively reduced increasing inflammation insulin resistance. Single-cell RNA/T...
T follicular helper (TFH) and 1 (Th1) cells generated after viral infections are critical for the control of infection development immunological memory. However, mechanisms that govern differentiation maintenance these two distinct lineages during remain unclear. We found viral-specific TFH Th1 showed reciprocal expression transcriptions factors TCF1 Blimp1 early infection, even before differential canonical marker CXCR5. Furthermore, was intrinsically required cell response to infection; in...
MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8 + T-cell response not well understood. Using an acute viral infection model, we show that microRNAs miR-17-92 cluster strongly induced after activation, down-regulated clonal expansion, further silenced during memory development. promotes cell-cycle progression effector T cells, its expression is critical to rapid expansion these cells. excessive enhances mammalian target...
The interactions between naphthol and bovine serum albumin (BSA) were investigated by spectroscopy. Our results prove the formation of complex BSA. Hydrophobic interaction dominates in association reaction. isomers stack with aromatic residues their binding sites different geometries. Effects BSA on excited-state proton transfer fluorescence spectra indicate characters sites. 1-Naphthol inserts deeply into a hydrophobic cavity whereas 2-naphthol is basic environment surface Naphthol...
Type I interferon–driven CD8 + T cells suppress neutralizing antibody production during chronic LCMV infection. See related Research Articles by Fallet et al. and Sammicheli a Focus Laidlaw
Abstract T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8 + antitumor function by restraining functional through epigenetic silencing of drivers terminal differentiation. enhances Polycomb repressor complex 2 (PRC2) activity indirectly promoting the expression PRC2-associated factor Phf19 downregulation Akt inhibitor, Ship1. orchestrates a transcriptional program extensively shared with restrain sustain responses....
Tuberous sclerosis complex human disease gene products TSC1 and TSC2 form a functional that negatively regulates target of rapamycin (TOR), an evolutionarily conserved kinase plays central role in cell growth metabolism. Here, we describe novel TSC1/2 controlling stem maintenance. We show the Drosophila ovary, disruption either Tsc1 or Tsc2 germline cells (GSCs) leads to precocious GSC differentiation loss. The loss can be rescued by treatment with TORC1 inhibitor rapamycin, eliminating S6K,...
Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5+ TCF1+ CD8+ cells that sustain during persistent proliferate upon anti-PD1 treatment. Approaches to expand these sought. We show blockade interferon type 1 (IFN-I) receptor leads expansion an IL-27– STAT1-dependent manner. IFNAR1 promoted accelerated division retention TCF1 virus-specific cells. found cell–intrinsic IL-27 signaling...
mTOR has important roles in regulation of both innate and adaptive immunity, but whether how modulates humoral immune responses have yet to be fully understood. To address this issue, we examined the effects rapamycin, a specific inhibitor mTOR, on B cell CD4 T during acute infection with lymphocytic choriomeningitis virus. Rapamycin treatment resulted suppression virus-specific by inhibiting proliferation germinal center (GC) cells. In contrast, number memory cells was increased...
Abstract Immunotherapy has made a significant impact in many tumors, including renal cell carcinoma (RCC). RCC been known to be immunoresponsive since the cytokine era of IFNα and IL2, but only small number patients had durable clinical benefit. Since then, discoveries key tumor drivers, as well an understanding contribution angiogenesis microenvironment (TME), led advances drug development, ultimately transforming patient outcomes. Combinations anti-angiogenic agents with immune checkpoint...
STING is an essential component of the innate immune system, yet homeostatic expression patterns and regulation are unknown. Using Sting1IRES-EGFP reporter conditional Sting1 transgenic mice, we found that critical for cell development functionality. was repressed in neutrophils, forced or signaling drove systemic inflammatory disease. During T lymphocyte development, restricted at double-positive stage via epigenetic silencing by DNA methyltransferase 1. Forced impaired independent type I...
ABSTRACT T cell aging increases the risk of viral infection‐related morbidity and mortality reduces vaccine efficacy in elderly. A major hallmark is loss quiescence shift toward terminal differentiation during homeostasis. However, how impacts program virus‐specific cells infection unclear. Here, a murine coronavirus (MHV) model with age‐associated increased mortality, we demonstrate that impairs, instead promoting, CD8 + cells. Upon infection, CD4 old mice showed marked reduction clonal...
The recently identified G-protein-coupled receptor GPR171 and its ligand BigLEN are thought to regulate food uptake anxiety. Though is commonly used as a T cell signature gene in transcriptomic studies, potential role immunity has not been explored. Here we show that transcribed cells protein expression induced upon antigen stimulation. neuropeptide interacts with suppress receptor-mediated signalling pathways inhibit proliferation. Loss of leads hyperactivity stimulation knockout mice...
Abstract Stimulator of Interferon Genes (STING) is a critical component the innate immune system. Mechanisms STING-mediated type I interferon (IFN-I) signaling during infection are well studied in myeloid cells. However, homeostatic STING expression patterns and their regulation, particularly lymphoid cells, unknown. We established Sting1IRES-EGFP reporter mouse to systematically characterize spatially tissues temporally along development Using this conditional Sting1 transgenic models, we...
Viral infections induce the differentiation of naive CD4 T cells into two distinct lineages, Th1 and follicular helper (TFH) cells. Two recent studies demonstrated that microRNA cluster miR-17-92 selectively promotes TFH responses. However, we show in this study expression is required for clonal expansion both virus-specific Upon viral infection, miR-17-92-deficient showed impaired subsequent memory formation. Although deficiency cells, was more affected. Overexpression resulted increased...
Patients with activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome (APDS) present sinopulmonary infections, lymphadenopathy, and cytomegalvirus (CMV) and/or Epstein-Barr virus (EBV) viremia, yet why patients fail to clear certain chronic viral infections remains incompletely understood. Using patient samples a mouse model (Pik3cdE1020K/+ mice), we demonstrate that, upon activation, Pik3cdE1020K/+ CD8+ T cells exhibit exaggerated features of effector populations both in vitro after...
During persistent antigen stimulation, exhausted CD8 + T cells are continuously replenished by self-renewing stem-like cells. However, how adapt to chronic stimulation remains unclear. Here, we show that primes chromatin for regulation the redox-sensing KEAP1-NRF2 pathway. Loss of KEAP1 in impaired control viral infection. cell–intrinsic suppressed NRF2 promote expansion and persistence virus-specific cells, drive a cell response, down-regulate immune checkpoint molecules, limit receptor...
Abstract The progressive decline of CD8 T cell effector function—also known as terminal exhaustion—is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive dysfunction remain poorly understood. Here, we report Kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid 2-related 2 (NRF2) signaling axis, which mediates cellular adaptations oxidative stress, directly regulates exhaustion. Transcriptional profiling dysfunctional cells from chronic...
Abstract Immunotherapy based on immune checkpoint blockade (ICB) has revolutionized cancer treatment. Immune cells, especially T play a crucial role in ICB. However, ICB- induced cell response remains incompletely investigated. Revealing landscape changes caused by ICB could promote the discovery of novel biomarkers with predictive efficacy and toxicity potential strategy to improve therapeutic while reducing side effects. We used single cell-based sequencing approaches analyze transcriptome...